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Genetics of Experimental Allergic Encephalomyelitis

  • Chapter
Experimental Models of Multiple Sclerosis

Abstract

The identification of genetic factors that control the pathogenetic pathways of autoimmune neuroinflammation and degeneration may provide targets for new therapeutic strategies in human diseases, such as multiple sclerosis. This is not easily accomplished as significant heterogeneity exists and such genetic dissection may more easily be performed using inbred rodent strains, where the genetic heterogeneity is avoided and variation in the environmental influences is minimized. Chronic relapsing experimental autoimmune encephalomyelitis (EAE) exhibits some histopathological features typical of multiple sclerosis and provides a tool to systemically identify genetic influences controlling susceptibility through genome scanning and selective breeding of congenic animals harbouring disease-related loci. As with MS, susceptibility is controlled by expression of certain major histocompatibility complex allotypes, which in EAE is in response to induction with certain myelin antigens. Both are complex polygenic diseases where disease traits are controlled by a number of polymorphic genes which individually exhibiting modest effect on disease course. A number of as yet largely unknown genes, cluster in certain regions that are sometimes shared between different strain combinations and are also shared by other inflammatory diseases, as they are uncovered the biology understood they may open avenues to treatment.

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References

  • Abdul-Majid K-B, Jirholt J, Stadelmann C, Stefferl A, Kjellen P, Wallstrom R, Holmdahl R, Lassmann H, Olsson T, Harris RA. q Screening of several H-2 congenic mouse strains identified H-2 mice as highly susceptible to MOG-induced EAE with minimal adjuvant requirement. Journal of Neuroimmunology 2000; 111: 23–33

    Article  PubMed  CAS  Google Scholar 

  • Akesson E, Oturai A, Berg J, Fredrikson S, Andersen O, Harbo HF, Laaksonen M, Myhr KM, Nyland HI, Ryder LP, Sandberg-Wollheim M, Sorensen PS, Spurkland A, Svejgaard A, Holmans P, Compston A, Hillert J, Sawcer S. A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis. Genes Immun. 2002;3:279–85.

    Article  PubMed  CAS  Google Scholar 

  • Amor, S., Groome, N., Linington, G, Morris, M.M., Dornmair, K., Gardinier, M.V., Matthieu, J.M., Baker, D. Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H J. Immunol. 1994; 153: 4349–4356.

    PubMed  CAS  Google Scholar 

  • Baker D, O’Neill JK, Gschmeissner SE, Wilcox CE, Butter C, Turk JL. Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice. J Neuroimmunol. 1990;28:261–70.

    Article  PubMed  CAS  Google Scholar 

  • Baker D, Rosenwasser OA, O’Neill JK, Turk JL. Genetic analysis of experimental allergic encephalomyelitis in mice. J Immunol. 1995; 155:4046–51.

    PubMed  CAS  Google Scholar 

  • Ban M, Stewart GJ, Bennetts BH, Heard R, Simmons R, Maranian M, Compston A, Sawcer SJ. A genome screen for linkage in Australian sibling-pairs with multiple sclerosis. Genes Immun. 2002; 3:464–9.

    Article  PubMed  CAS  Google Scholar 

  • Barcellos LF, Thomson G, Carrington M, Schafer J, Begovich AB, Lin P, Xu XH, Min BQ, Marti D, Klitz W: Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis. Evidence of a new susceptibility locus in Caucasian and Chinese patients. JAMA 1997, 278:1256–1261

    Article  PubMed  CAS  Google Scholar 

  • Barry R, Bolton C, Glynn P, Groome N. Myelin basic protein peptides in urine. Ann Neurol. 1992; 31:345–8.

    Article  PubMed  CAS  Google Scholar 

  • Becanovic K, Backdahl L, Wallstrom E, Aboul-Enein F, Lassmann H, Olsson T, Lorentzen JC. Paradoxical effects of srthritis-regulating chromosome 4 rgions on myelin oligodendrocyte glycoprotein induced. Eur J Immunol. 2003a;33:19076–16.

    Article  CAS  Google Scholar 

  • Becanovic K, Wallstrom E, Kornek B, Glaser A, Broman KW, Dahlman I, Olofsson P, Holmdahl R, Luthman H, Lassmann H, Olsson T. New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J Immunol. 2003b;170:1062–9.

    PubMed  CAS  Google Scholar 

  • Bergsteinsdottir K, Yang HT, Pettersson U, Holmdahl R. Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis. J Immunol. 2000: 164:1564–8.

    PubMed  CAS  Google Scholar 

  • Bjartmar C, Wujek JR, Trapp BD. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 2003;206:165–71.

    Article  PubMed  CAS  Google Scholar 

  • Blankenhorn E P, Butterfield RJ, Rigby R, Cort L, Giambrone D, McDermott R, McEntee K, Solowski N, Meeker ND, Zachary JF, Doerge RW, Teuscher C: Genetic analysis of the influence of pertussis toxin on EAE susceptibility: an environmental agent can override genetic checkpoints. J Immunol 2000, 164:3420–3425

    PubMed  CAS  Google Scholar 

  • Bebo BF Jr, Zelinka-Vincent E, Adamus G, Amundson D, Vandenbark AA, Offner H: Gonadal hormones influence the immune response to PLP 139–151 and the clinical course of relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol 1998, 84:122–130

    Article  PubMed  CAS  Google Scholar 

  • Bebo BF Jr, Schuster JC, Vandenbark AA, Offner H: Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells. J Immunol 1999, 162:35–40

    PubMed  CAS  Google Scholar 

  • Bettelli E, Pagany M, Weiner HL, Linington C, Sobel RA, Kuchroo VK. oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med. 2003; 197:1073–81.

    Article  PubMed  CAS  Google Scholar 

  • Brabb T, Goldrath AW, von Dassow P, Paez A, Liggitt HD, Goverman J Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis. J Immunol. 1997;159:497–507.

    PubMed  CAS  Google Scholar 

  • Brahic M, Bureau JF. Genetics of susceptibility to Theiler’s virus infection. Bioessays. 1998; 20:627–33.

    Article  PubMed  CAS  Google Scholar 

  • Broadley S, Sawcer S, D’Alfonso S, Hensiek A, Coraddu F, Gray J, Roxburgh R, Clayton D, Buttinelli C, Quattrone A, Trojano M, Massacesi L, Compston A. A genome screen for multiple sclerosis in Italian families. Genes Immun. 2001; 2:205–10

    Article  PubMed  CAS  Google Scholar 

  • Brocke S, Gijbels K, Steinman L: Experimental autoimmune encephalomyelitis in the mouse. Autoimmune Disease Models, a Guidebook. Edited by IR Cohen, A Miller. New York, Academic Press, 1994, pp1–14

    Google Scholar 

  • Brok HP, Bauer J, Jonker M, Blezer E, Amor S, Bontrop RE, Laman JD, ’t Hart BA. Non-human primate models of multiple sclerosis. Immunol Rev. 2001; 183:173–85.

    Article  PubMed  CAS  Google Scholar 

  • Butterfield RJ, Sudweeks JD, Blankenhorn EP, Korngold R, Marini JC, Todd JA, Roper RJ, Teuscher C: New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice. J Immunol 1998, 161:1860–1867

    PubMed  CAS  Google Scholar 

  • Butterfield RJ, Blankenhorn EP, Roper RJ, Zachary JF, Doerge RW, Sudweeks J, Rose J, Teuscher C: Genetic analysis of disease subtypes and sexual dimorphisms in mouse experimental allergic encephalomyelitis (EAE): relapsing/remitting and monophasic remitting/ nonrelapsing EAE are immunogenetically distinct. J Immunol 1999, 162:3096–3102

    PubMed  CAS  Google Scholar 

  • Butterfield RJ, Blankenhorn EP, Roper RJ, Zachary JF, Doerge RW, Teuscher C. Identification of genetic loci controlling the characteristics and severity of brain and spinal cord lesions in experimental allergic encephalomyelitis. Am. J. Pathol. 2000; 157:637–645.

    PubMed  CAS  Google Scholar 

  • Bruno R, Sabater L, Sospedra M, Ferrer-Francesch X, Escudero D, Martinez-Caceres E, Pujol-Borrell R. Multiple sclerosis candidate autoantigens except myelin oligodendrocyte glycoprotein are transcribed in human thymus. Eur J Immunol. 2002; 32:2737–47.

    Article  PubMed  CAS  Google Scholar 

  • Chataway, J., Feakes, R., Coraddu, F., Gray, J., Deans, J., Fraser, M., Robertson, N., Broadley, S., Jones, H., Clayton, D., Goodfellow, P., Sawcer, S., Compston, A., The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen. Brain, 1998; 121, 1869–1887.

    Article  PubMed  Google Scholar 

  • Compston A, Coles A. Multiple sclerosis. Lancet 2002; 359: 1221–1231.

    Article  PubMed  Google Scholar 

  • Compston A, Sawcer S. Genetic analysis of multiple sclerosis. Curr Neurol Neurosci Rep. 2002;2:259–66.

    Article  PubMed  Google Scholar 

  • Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000; 343: 1430–38.

    Article  PubMed  CAS  Google Scholar 

  • Coraddu F, Sawcer S, Feakes R, Chataway J, Broadley S, Jones HB, Clayton D, Gray J, Smith S, Taylor C, Goodfellow PN, Compston A. HLA typing in the United Kingdom multiple sclerosis genome screen. Neurogenetics. 1998; 2:24–33.

    Article  PubMed  CAS  Google Scholar 

  • Coraddu F, Sawcer S, D’Alfonso S, Lai M, Hensiek A, Solla E, Broadley S, Mancosu C, Pugliatti M, Marrosu MG, Compston A. A genome screen for multiple sclerosis in Sardinian multiplex families. Eur J Hum Genet. 2001;9:621–6.

    Article  PubMed  CAS  Google Scholar 

  • Croxford JL, O’Neill JK, Baker D. Polygenic control of experimental allergic encephalomyelitis in Biozzi ABH and BALB/c mice. J Neuroimmunol. 1997; 74:205–11.

    Article  PubMed  CAS  Google Scholar 

  • Dalai M, Kim S, Voskuhl RR: Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol 1997,159:3–6

    Google Scholar 

  • Dahlman I, Lorentzen JC, de Graaf KL, Stefferl A, Linington C, Luthman H, Olsson T. Quantitative trait loci disposing for both experimental arthritis and encephalomyelitis in the DA rat; impact on severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis and antibody isotype pattern. Eur J Immunol. 1998; 28:2188–96.

    Article  PubMed  CAS  Google Scholar 

  • Dahlman I, Jacobsson L, Glaser A, Lorentzen JC, Andersson M, Luthman H, Olsson T. Genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9. J Immunol. 1999a;162:2581–8

    PubMed  CAS  Google Scholar 

  • Dahlman I, Wallstrom E, Weissert R, Storch M, Kornek B, Jacobsson L, Linington C, Luthman H, Lassmann H, Olsson T. Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18. Hum Mol Genet. 1999b;8:2183–90.

    Article  PubMed  CAS  Google Scholar 

  • Duquette P, Pleines J, Girard M, Charest L, Senecal-Quevillon M, Masse C: The increased susceptibility of women to multiple sclerosis. Can J Neurol Sci 1992, 19:466–471

    PubMed  CAS  Google Scholar 

  • Ebers GC, Sadovnick AD, Risch NJ: A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 1995, 377:150–151

    Article  PubMed  CAS  Google Scholar 

  • Ebers GC, Kukay K, Bulman DE, Sadovnick AD, Rice G, Anderson C, Armstrong H, Cousin K, Bell RB, Hader W, Paty DW, Hashimoto S, Oger J, Duquette P, Warren S, Gray T, O’Connor P, Nath A, Auty A, Metz L, Francis G, Paulseth JE, Murray TJ, Pryse-Phillips W, Risch N: A full genome search in multiple sclerosis. Nat Genet 1996, 13:472–476.

    Article  PubMed  CAS  Google Scholar 

  • Encinas, JA, Lees MB, Sobel RA, Symonowics C, Greer JM, Shovlin CL, Weiner HL, Seidman CE, Seidman JG, Kuchroo VJ. Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/L and B10.S mice. J. Immunol. 1996; 157:2186.

    PubMed  CAS  Google Scholar 

  • Encinas JA, Wicker LS, Peterson LB, Mukasa A, Teuscher C, Sobel R, Weiner HL, Seidman CE, Seidman JG, Kuchroo VK: QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15 cM region containing I12. Nat Genet 1999,21:158–160.

    Article  PubMed  CAS  Google Scholar 

  • Encinas JA, Kuchroo VK. Mapping and identification of autoimmunity genes Curr Opin Immunol. 2000;12:691–7.

    Article  PubMed  CAS  Google Scholar 

  • Encinas, JA, Lees MB, Sobel RA, Symonowics C, Weiner HL, Seidman CE, Seidman JG, Kuchroo VJ. Identification of genetic loci associated with paralysis, inflammation and weight loss in mouse experimental autoimmune encephalomyelitis. Int. Immunol. 2001; 13:257–64

    Article  PubMed  CAS  Google Scholar 

  • Feakes R, Sawcer S, Smillie B, Chataway J, Broadley S, Compston A. No evidence for the involvement of interleukin 2 or the immunoglobulin heavy chain gene cluster in determining genetic susceptibility to multiple sclerosis. J Neurol Neurosurg Psychiatry. 2000; 68:679.

    Article  PubMed  CAS  Google Scholar 

  • Fritz, RB, Skeen MJ, Chou CH, Garcia M, Egorov IK. Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J. Immunol. 1985; 134:2328–2332.

    PubMed  CAS  Google Scholar 

  • Furlan R, Brambilla E, Sanvito F, Roccatagliata L, Olivieri S, Bergami A, Pluchino S, Uccelli A, Comi G, Martino G. Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice. Brain. 2003;126:285–91.

    Article  PubMed  Google Scholar 

  • Gao JF, Call SB, Fillmore PD, Watanabe T, Meeker ND, Teuscher C. Analysis of the role of Bphs/Hrhl in the genetic control of responsiveness to pertussis toxin. Infect Immun. 2003;71:1281–7.

    Article  PubMed  CAS  Google Scholar 

  • Goedde R, Sawcer S, Boehringer S, Miterski B, Sindern E, Haupts M, Schimrigk S, Compston A, Epplen JT. A genome screen for linkage disequilibrium in HLA-DRB1*15-positive Germans with multiple sclerosis based on 4666 microsatellite markers. Hum Genet. 2002; 111:270–7.

    Article  PubMed  CAS  Google Scholar 

  • Goverman J, Woods A, Larson L, Weiner LP, Hood L, Zaller DM Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell. 1993;72:551–60.

    Article  PubMed  CAS  Google Scholar 

  • Haines JL, Ter Minassian M, Bazyk A, Gusella JF, Kim DJ, Terwedow H, Pericak-Vance MA, Rimmler JB, Haynes CS, Roses AD, Lee A, Shaner B, Menold M, Seboun E, Fitoussi RP, Gartioux C, Reyes C, Ribierre F, Gyapay G, Weissenbach J, Hauser SL, Goodkin DE, Lincoln R, Usuku K, Oksenberg JR: A complete genomic screen for multiple sclerosis underscores a role for the major histocompatibility complex. The Multiple Sclerosis Genetics Group. Nat Genet 1996, 13:469–471

    Article  PubMed  CAS  Google Scholar 

  • Hensiek AE, Sawcer SJ, Feakes R, Deans J, Mander A, Akesson E, Roxburgh R, Coraddu F, Smith S, Compston DA. HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002; 72:184–7.

    Article  PubMed  CAS  Google Scholar 

  • Hogancamp WE, Rodriguez M, Weinshenker BG: The epidemiology of multiple sclerosis. Mayo Clin Proc 1997, 72:871–878

    Article  PubMed  CAS  Google Scholar 

  • Homo-Delarche F, Fitzpatrick F, Christeff N, Nunez EA, Bach JF, Dardenne M: Sex steroids, glucocorticoids, stress and autoimmunity. J Steroid Biochem Mol Biol 1991, 40:619–637

    Article  PubMed  CAS  Google Scholar 

  • Ichikawa M, Koh CS, Inaba Y, Seki C, Inoue A, Itoh M, Ishihara Y, Bernard CC, Komiyama A. IgG subclass switching is associated with the severity of experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide in NOD mice. Cell Immunol. 1999; 191:97–104.

    Article  PubMed  CAS  Google Scholar 

  • Jansson L, Holmdahl R. Estrogen-mediated immunosuppression in autoimmune diseases. Inflamm. res. 1998, 47:290–301

    Article  PubMed  CAS  Google Scholar 

  • Jirholt, J., A.-K. Lindqvist, J. Karlsson, A. Andersson, and R. Holmdahl. Identification of susceptibility genes for experimental autoimmune encephalomyelitis that overcome the effect of protective alleles at the eae2 locus. Int. Immunol. 2002;14:79–85

    Article  PubMed  CAS  Google Scholar 

  • Karlsson J, Zhao, Lonskaya I, Neptin M, Holmdahl R, Andersson A. Novel quantitative trait loci controlling development of experimental autoimmune encephalomyelitis and proportion of lymphocyte subpopulations. J. Immunol 2003 170:1019–1026

    PubMed  CAS  Google Scholar 

  • Kira J, Kanai T, Nishimura Y, Yamasaki K, Matsushita S, Kawano Y, Hasuo K, Tobimatsu S, Kobayashi T: Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders. Ann Neurol 1996, 40:569–574

    Article  PubMed  CAS  Google Scholar 

  • Kjellén P, Jansson, Vestberg M, A Andersson, Mattsson R, Holmdahl. The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein 103–116 J. Neuroimmunol. 2001; 120:25–33

    Article  PubMed  Google Scholar 

  • Kojima K, Berger T, Lassmann H, Hinze-Selch D, Zhang Y, Gehrmann J, Reske K, Wekerle H, Linington C. Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100 beta molecule, a calcium binding protein of astroglia. J Exp Med. 1994; 180:817–29.

    Article  PubMed  CAS  Google Scholar 

  • Kuokkanen S, Gschwend M, Rioux JD, Daly MJ, Terwilliger JD, Tienari PJ, Wikstrom J, Palo J, Stein LD, Hudson TJ, Lander ES, Peltonen L: Genomewide scan of multiple sclerosis in Finnish multiplex families. Am J Hum Genet 1997, 61:1379–1387

    Article  PubMed  CAS  Google Scholar 

  • Kuokkanen S, Sundvall M, Terwilliger JD, Tienari PJ, Wikstrom J, Holmdahl R, Pettersson U, Peltonen L. A putative vulnerability locus to multiple sclerosis maps to 5pl4-pl2 in a region syntenic to the murine locus Eae2. Nat Genet 1996, 13:477–480

    Article  PubMed  CAS  Google Scholar 

  • Kuchroo VK, Anderson AC, Waldner H, Munder M, Bettelli E, Nicholson LB. T cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Annu Rev Immunol. 2002;20:101–23.

    Article  PubMed  CAS  Google Scholar 

  • Larsen F, Oturai A, Ryder LP, Madsen HO, Hillert J, Fredrikson S, Sandberg-Wollheim M, Laaksonen M, Harbo HF, Sawcer S, Fugger L, Sorensen PS, Svejgaard A. Linkage analysis of a candidate region in Scandinavian sib pairs with multiple sclerosis reveals linkage to chromosome 17q. Genes Immun. 2000; 1:456–9.

    Article  PubMed  CAS  Google Scholar 

  • Levine S, Sowinski R. Experimental allergic encephalomyelitis in inbred and outbred mice. J Immunol. 1973; 110:139–43.

    PubMed  CAS  Google Scholar 

  • Li Y, Li H, Martin R, Mariuzza RA. Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins. J Mol Biol. 2000;304:177–88.

    Article  PubMed  CAS  Google Scholar 

  • Lublin FD, Reingold SC: Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996, 46:907–911

    PubMed  CAS  Google Scholar 

  • Lucchinetti CF, Bruck W, Rodriguez M, Lassmann H: Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 1996, 6:259–274

    PubMed  CAS  Google Scholar 

  • Lyons PA, Armitage N, Argentina F, Denny P, Hill NJ, Lord CJ, Wilusz MB, Peterson LB, Wicker LS, Todd JA. Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of mouse chromosome 3: identification of a candidate segment of ancestral DNA by haplotype mapping. Genome Res. 2000;10:446–53.

    Article  PubMed  CAS  Google Scholar 

  • Lyons PA, Armitage N, Lord CJ, Phillips MS, Todd JA, Peterson LB, Wicker LS. Mapping by genetic interaction: high-resolution congenic mapping of the type 1 diabetes loci Iddl0 and Iddl8 in the NOD mouse. Diabetes. 2001; 50:2633–7.

    Article  PubMed  CAS  Google Scholar 

  • Ma RZ, Gao J, Meeker ND, Fillmore PD, Tung KS, Watanabe T, Zachary JF, Offner H, Blankenhorn EP, Teuscher C. Identification of Bphs, an autoimmune disease locus, as histamine receptor H1. Science. 2002;297:620–3.

    Article  PubMed  CAS  Google Scholar 

  • Madsen LS, Andersson EC, Jansson L, krogsgaard M, Andersen CB, Engberg J, Strominger JL, Svejgaard A, Hjorth JP, Holmdahl R, Wucherpfennig KW, Fugger L. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat Genet. 1999;23:343–7.

    Article  PubMed  CAS  Google Scholar 

  • Marrosu MG, Murru MR, Costa G, Cucca F, Sotgiu S, Rosati G, Muntoni F. Multiple sclerosis in Sardinia is associated and in linkage disequilibrium with HLA-DR3 and-DR4 alleles. Am J Hum Genet. 1997;61:454–7.

    Article  PubMed  CAS  Google Scholar 

  • Mendel I, Kerlero de Rosbo N, Ben-Nun A. A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: fine specificity and T cell receptor V beta expression of encephalitogenic cells. Eur. J. Immunol. 1995; 25: 1951–1959.

    Article  PubMed  CAS  Google Scholar 

  • Mendel I, Gur H, Kerlero de Rosbo N, Ben-Nun A. Experimental autoimmune encephalomyelitis induced in B6.C-H-2bml2 mice by myelin oligodendrocyte glycoprotein: effect of MHC class II mutation on immunodominant epitope selection and fine epitope specificity of encephalitogenic T cells. J Neuroimmunol. 1999;96:9–20.

    Article  PubMed  CAS  Google Scholar 

  • Merriman TR, Cordell HJ, Eaves IA, Danoy PA, Coraddu F, Barber R, Cucca F, Broadley S, Sawcer S, Compston A, Wordsworth P, Shatford J, Laval S, Jirholt J, Holmdahl R, Theofilopoulos AN, Kono DH, Tuomilehto J, Tuomilehto-Wolf E, Buzzetti R, Marrosu MG, Undlien DE, Ronningen KS, Ionesco-Tirgoviste C, Shield JP, Pociot F, Nerup J, Jacob CO, Polychronakos C, Bain SC, Todd JA. Suggestive evidence for association of human chromosome 18ql2-q21 and its orthologue on rat and mouse chromosome 18 with several autoimmune diseases. Diabetes. 2001;50:184–94.

    Article  PubMed  CAS  Google Scholar 

  • Morris-Downes MM, McCormack K, Baker D, Sivaprasad D, Natkunarajah J, Amor S. Encephalitogenic and immunogenic potential of myelin-associated glycoprotein (MAG), oligodendrocyte-specific glycoprotein (OSP) and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) in ABH and SJL mice. J Neuroimmunol. 2002; 122:20–33.

    Article  PubMed  CAS  Google Scholar 

  • Olerup O, Hillert J, Fredrikson S, Olsson T, Kam-Hansen S, Moller E, Carlsson B, Wallin J: Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities. Proc Natl Acad Sci USA 1989, 86:7113–7117

    Article  PubMed  CAS  Google Scholar 

  • Olsson T, Dahlman I, Wallström E, Weissert R, Piehl F. Genetics of rat Neuroinflammation. J. Neuroimmunol 2000; 107:191–200

    Article  PubMed  CAS  Google Scholar 

  • O’Neill JK, Baker D, Davison AN, Allen SJ, Butter C, Waldmann H, Turk JL. Control of immune-mediated disease of the central nervous system with monoclonal (CD4-specific) antibodies. J Neuroimmunol. 1993; 45:1–14.

    Article  PubMed  CAS  Google Scholar 

  • Oturai A, Larsen F, Ryder LP, Madsen HO, Hillert J, Fredrikson S, Sandberg-Wollheim M, Laaksonen M, Koch-Henriksen N, Sawcer S, Fugger L, Sorensen PS, Svejgaard A. Linkage and association analysis of susceptibility regions on chromosomes 5 and 6 in 106 Scandinavian sibling pair families with multiple sclerosis. Ann Neurol. 1999; 46:612–6.

    Article  PubMed  CAS  Google Scholar 

  • Pagany M, Jagodic M, Bourquin C, Olsson T, Linington C. Genetic variation in myelin oligodendrocyte glycoprotein expression and susceptibility to experimental autoimmune encephalomyelitis. J Neuroimmunol. 2003;139:1–8.

    Article  PubMed  CAS  Google Scholar 

  • Pihlaja H, Rantamaki T, Wikstrom J, Sumelahti ML, Laaksonen M, Ilonen J, Ruutiainen J, Pirttila T, Elovaara I, Reunanen M, Kuokkanen S, Peltonen L, Koivisto K, Tienari PJ. Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland. Genes Immun. 2003; 4:138–46.

    Article  PubMed  CAS  Google Scholar 

  • Podolin PL, Denny P, Lord CJ, Hill NJ, Todd JA, Peterson LB, Wicker LS, Lyons PA. Congenic mapping of the insulin-dependent diabetes (Idd) gene, Iddl0, localizes two genes mediating the Iddl0 effect and eliminates the candidate Fcgrl. J Immunol. 1997;159:1835–43.

    PubMed  CAS  Google Scholar 

  • Podolin PL, Wilusz MB, Cubbon RM, Pajvani U, Lord CJ, Todd JA, Peterson LB, Wicker LS, Lyons PA. Differential glycosylation of interleukin 2, the molecular basis for the NOD Idd3 type 1 diabetes gene? Cytokine. 2000; 12:477–82.

    Article  PubMed  CAS  Google Scholar 

  • Prins JB, Todd JA, Rodrigues NR, Ghosh S, Hogarth PM, Wicker LS, Gaffney E, Podolin PL, Fischer PA, Sirotina A, et al. Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. Science. 1993;260:695–8.

    Article  PubMed  CAS  Google Scholar 

  • Raine CS, Barnett LB, Brown A, Behar T, McFarlin DE: Neuropathology of experimental allergic encephalomyelitis in inbred strains of mice. Lab Invest 1980, 43:150–157

    PubMed  CAS  Google Scholar 

  • Reboul J, Mertens C, Levillayer F, Eichenbaum-Voline S, Vilkoren T, Cournu I, Babron MC, Lyon-Caen O, Clerget-Darpoux F, Edan G, Clanet M, Brahic M, Bureau JF, Fontaine B, Liblau R. Cytokines in genetic susceptibility to multiple sclerosis: a candidate gene approach. French Multiple Sclerosis Genetics Group. J Neuroimmunol 2000, 102:107–112.

    Article  PubMed  CAS  Google Scholar 

  • Roth MP, Viratelle C, Dolbois L, Delverdier M, Borot N, Pelletier L, Druet P, Clanet M, Coppin H. A genome-wide search identifies two susceptibility loci for experimental autoimmune encephalomyelitis on rat chromosomes 4 and 10. J Immunol. 1999;162:1917–22.

    PubMed  CAS  Google Scholar 

  • Sadlack B, Lohler J, Schorle H, Klebb G, Haber H, Sickel E, Noelle RJ, Horak I. Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur J Immunol. 1995;25:3053–9.

    Article  PubMed  CAS  Google Scholar 

  • Sawcer S, Jones HB, Feakes R, Gray J, Smaldon N, Chataway J, Robertson N, Clayton D, Goodfellow PN, Compston A: A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nat Genet 1996, 13:464–468

    Article  PubMed  CAS  Google Scholar 

  • Sawcer S, Maranian M, Setakis E, Curwen V, Akesson E, Hensiek A, Coraddu F, Roxburgh R, Sawcer D, Gray J, Deans J, Goodfellow PN, Walker N, Clayton D, Compston A. A whole genome screen for linkage disequilibrium in multiple sclerosis confirms disease associations with regions previously linked to susceptibility. Brain. 2002; 125:1337–47.

    Article  PubMed  Google Scholar 

  • Seboun E, Oksenberg JR, Rombos A, Usuku K, Goodkin DE, Lincoln RR, Wong M, Pham-Dinh D, Boesplug-Tanguy O, Carsique R, Fitoussi R, Gartioux C, Reyes C, Ribierre F, Faure S, Fizames C, Gyapay G, Weissenbach J, Dautigny A, Rimmler JB, Garcia ME, Pericak-Vance MA, Haines JL, Hauser SL. Linkage analysis of candidate myelin genes in familial multiple sclerosis. Neurogenetics. 1999; 2:155–62.

    Article  PubMed  CAS  Google Scholar 

  • Slavin A, Ewing C, Liu J, Ichikawa M, Slavin J, Bernard CC. Induction of a multiple sclerosis-like disease in mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein. Autoimmunity. 1998;28:109–20.

    PubMed  CAS  Google Scholar 

  • Sudweeks JD, Todd JA, Blankenhorn EP, Wardell BB, Woodward SR, Meeker ND, Estes SS, Teuscher C: Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6. Proc Natl Acad Sci USA 1993, 90:3700–3704

    Article  PubMed  CAS  Google Scholar 

  • Sun D, Whitaker JN, Huang Z, Liu D, Coleclough C, Wekerle H, Raine CS. Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. J Immunol. 2001; 166:7579–87

    PubMed  CAS  Google Scholar 

  • Sundvall, M, Jirholt J, Yang HT, Jansson L, Engstrom A, Pettersson U, Holmdahl R. Identification of murine loci associated with susceptibility to chronic experimental autoimmune encephalomyelitis. Nat. Genet. 1995, 10:313–317.

    Article  PubMed  CAS  Google Scholar 

  • Teuscher C, Butterfield RJ, Ma RZ, Zachary JF, Doerge RW, Blankenhorn EP: Sequence polymorphisms in the chemokines Scyal(TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-l), and Scyal2 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis. J Immunol 1999, 163:2262–2266

    PubMed  CAS  Google Scholar 

  • t’Hart B, Amor S. The use of animal models to investigate the pathogenesis of neuroinflammatory disorders of the central nervous sysyem. Curr Opin Neurol. 2003;16:375–384

    Article  Google Scholar 

  • Thompson AJ, Polman CH, Miller DH, McDonald WI, Brochet B, Filippi MMX, De Sa J: Primary progressive multiple sclerosis. Brain 1997, 120:1085–1096

    Article  PubMed  Google Scholar 

  • Thorpe JW, Kidd D, Moseley IF, Thompson AJ, MacManus DG, Compston DA, McDonald WI, Miller DH: Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI. Brain 1996, 119:709–714

    Article  PubMed  Google Scholar 

  • Todd, JA, Aitman TJ, Cornall RJ, Ghosh S, Hall JRS, Hearne CM, Knight AM, Love JM, McAleer MA, Prins J-B, Rodrigues N, Lathrop M, Pressey A, DeLarato NH, Peterson LB, Wicker LS. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature. 1991;351:542–547.

    Article  PubMed  CAS  Google Scholar 

  • Tuohy VK, Sobel RA, Lees MB: Myelin proteolipid protein-induced experimental allergic encephalomyelitis. Variations of disease expression in different strains of mice. J Immunol 1988, 140:1868–1873

    PubMed  CAS  Google Scholar 

  • Wekerle H, Kojima K, Lannes-Vieira J, Lassmann H, Linington C: Animal models. Ann Neurol 1994, 36:S47–S53

    Article  PubMed  CAS  Google Scholar 

  • Wujek JR, Bjartmar C, Richer E, Ransohoff RM, Yu M, Tuohy VK, Trapp BD. Axon loss in the spinal cord determines permanent neurological disability in an animal model of multiple sclerosis. J Neuropathol Exp Neurol 2002; 61: 23–32.

    PubMed  Google Scholar 

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Baker, D. (2005). Genetics of Experimental Allergic Encephalomyelitis. In: Lavi, E., Constantinescu, C.S. (eds) Experimental Models of Multiple Sclerosis. Springer, Boston, MA. https://doi.org/10.1007/0-387-25518-4_10

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